Many bacterial small RNAs (sRNAs) modulate gene expression by base-pairing with target mRNAs (1). Trans-encoded sRNAs regulate mRNA expression through small, discontinuous seed-pairings' which are usually at or near the translation initiation signals (TIS) of their targets, whereas cis-antisense sRNAs (asRNAs) are encoded on the DNA strand opposite to that of their targets (2). In the cellular transcript overflow, each of these base-pairing sRNAs has to efficiently locate and bind to its mRNA target, recognizing these through high-affinity contacts made by a few accessible nucleotides. These are usually situated in single-strands (i.e. C-rich stretches), in loops of the regulator, in the target(s), or in both places. After this primary interaction, the structure of the two RNAs is generally rearranged and additional base pairs are formed. In Gram-negative bacteria, the Hfq RNA-binding protein is usually required for transencoded sRNA stability and operation (2). Hfq facilitates sRNA-mRNA base-pairing by binding both RNAs simultaneously and/or by changing one or both of the RNA structures (3), but its exact contribution at a molecular level remains, for the most part, unresolved.
RydC is a trans-encoded sRNA expressed by enteric bacteria that folds as a pseudoknot and interacts with Hfq, a protein that positively influences sRNA stability in vivo (4). In Escherichia coli, RydC controls yejABEF mRNA expression producing an inner membrane ABC transporter (4). yejABEF allows the uptake of translation inhibitor microcin C, a peptide-nucleotide antibiotic targeting aspartyl-tRNA synthetase (5). In Salmonella, the yej operon is involved in virulence, interferes with MHC I presentation, counteracts antimicrobial peptides, and provides a nutritious peptide source for survival and proliferation inside the host (6). In intracellular Salmonella typhimurium, RydC expression is repressed (7), and perhaps, as is the case for E. coli, this is to reduce nutrient uptake by lowering yej mRNA levels (4). In Salmonella, RydC selectively activates the longer isoform of the cyclopropane fatty acid synthase mRNA in order to regulate membrane stability (8).
Many bacteria switch between a single-cell motile lifestyle and multi-cellular, sessile adhesive states forming biofilm, resulting in a protected growth mode which allows cells to survive and thrive in hostile environments (9). Biofilm formation is a complex process involving numerous sensory signals linked to elaborate gene regulations via a transcription factor array. When enteric bacteria construct biofilms, they involve curli-specific genes (csg) organised in the csgDEFG and csgBAC bicistronic operon. csgEFG is required for export, and CsgD is a member of the LuxR family of transcriptional regulators that activate csgBA to synthesize the structural components of curli fimbriae. CsgD governs the synthesis of the extracellular matrix components cellulose and curli fimbriae in enteric bacteria responsible for the ‘rdar’ morphotype (10). A collection of environmental alerts adjust CsgD expression, causing it to swap from a mobile to an attached mode (11). The csgD promoter is positively regulated by several transcription factors (11) and by small signalling molecules (12), whereas its expression is negatively controlled at the posttranscriptional level by five sRNAs acting in collaboration with Hfq. In response to various environmental signals, OmrA/B (13), McaS (14), RprA (15), and GcvB (16) all downregulate CsgD translation by binding at specific locations onto the csgD mRNA 5′ untranslated region (UTR), which is a signal perception platform (17).
Accordingly, there is a need to develop new compounds that will be suitable for inhibiting bacterial adhesion and aggregation and biofilms formation, and new drugs that will be suitable for preventing or treating infection from a biofilm. In this way, it has been suggested that characterization of new anti-bacterial compounds for inhibiting bacterial adhesion and aggregation and biofilms formation and for treatment or prevention of infection from a biofilm may be highly desirable.
There is no disclosure in the art of the role of RydC in bacterial adhesion, aggregation and biofilms formation, nor the use of RydC in the prevention or treatment of infection from a biofilm.